This paper demonstrates that ARMS is critical to the normal maintenance of cortical neurons and spatial memory in the adult mouse. It appears to be most important to entorhinal and frontal cortical neurons, because large areas within these regions exhibited signs of oxidative stress, such as weak labeling with the antibody NeuN, damaged mitochondria, and defects in myelin. This is interesting because these areas are critical to cognition and have been shown to be vulnerable in aging and Alzheimer’s disease. This study supports the hypothesis that neurotrophins are critical to normal aging, and suggest that ARMS could be a useful therapeutic target.